This project is designed to advance the understanding of axon regeneration in the context of cervical spinal cord injury (SCI) and to evaluate a novel approach to enhance recovery. Our published work demonstrate that following trauma to the dorsal (sensory) root that gene transfer to dorsal root ganglion (DRG) neurons using nonreplicating recombinant herpes simplex virus (HSV)-based vectors can enhance sensory axonal regeneration and that HSV-mediated gene transfer to the DRG can reduce below-level neuropathic pain following SCI and after proximal root injury. The proposed study will exploit advances in our laboratory in the development of recombinant non-replicating genomic HSV-based vectors for gene transfer to the nervous system to test the hypothesis that HSV-mediated delivery of C3 transferase gene alone or in combination with the gene for the neurotrophin artemin to the DRG from skin inoculation can be used to enhance sensory axon regeneration and improve sensory behavioral outcomes after cervical SCI, thereby mitigating functional disability. The experiments outlined in this proposal exploit the unique properties of HSV-based vectors to provide local delivery of bioactive peptides to the extending tip of injured axons. These studies will advance understanding of the basic biology underlying recovery in SCI while testing a therapeutic intervention that could be applied to the treatment of Veteran patients.